Modification: PSEN1: Knock-Out
Disease Relevance: Alzheimer's Disease
Strain Name: B6.129-Psen1tm1Shn/J
Genetic Background: C57BL/6
Availability: The Jackson Lab: Stock# 003615; Cryopreserved
These mice are deficient in PSEN1. This model is perinatal lethal in homozygouse animals which die shortly after birth, presumably from breathing difficulties due to ribcage deformity (Shen et al., 1997).
Gross skeletal malformations and central nervous system abnormalities are observed in these animals. Additional phenotypes include: shortened tails that curve to the right, thickened necks, loose skin, hind limbs that curve towards the midline, and reduced body weight.
Brain development is abnormal. By embryonic day 9.5 there is a drastic reduction in neural progenitor cells and the ventricular zone is markedly thinner by embryonic day 14.5. Later, hemorrhages occur in the CNS with variable onset times, locations, and severity. Bilaterial cerebral cavitation caused by massive neuronal loss in specific brain regions is prominent after embryonic day 16.5, primarily in the ventrolateral region of the ventricular zone (Shen et al., 1997).
A targeting construct containing a neomycin cassette was used to disrupt exons 2 and 3 of the endogenous mouse PS1 gene.
The Jackson Lab: Stock# 003822
- Shen J, Bronson RT, Chen DF, Xia W, Selkoe DJ, Tonegawa S. Skeletal and CNS defects in Presenilin-1-deficient mice. Cell. 1997 May 16;89(4):629-39. PubMed.
No Available Further Reading